Regulation of neutrophil myeloperoxidase inhibitor SPIN by the small RNA Teg49 in Staphylococcus aureus,Molecular Microbiology

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Regulation of neutrophil myeloperoxidase inhibitor SPIN by the small RNA Teg49 in Staphylococcus aureus
Molecular Microbiology ( IF 2.6 ) Pub Date : 2022-05-16 , DOI: 10.1111/mmi.14919
Liviu Cengher ₁ , Adhar C Manna ₁ , Junho Cho ₁ , Jomkuan Theprungsirikul ₁ , Katherine Sessions ₁ , William Rigby ₁ , Ambrose L Cheung ₁

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Teg49 is a Staphylococcus aureus trans-acting regulatory sRNA derived from cleavage of the sarA P3 transcript. We showed by RNA-Seq here that the 5′ trident-like structure in Teg49 regulates transcriptionally (direct and indirect) 22 genes distinct from sarA. Among these, Teg49 was noted to repress spn, encoding a 102 residue preprotein which yields the mature 73 residue peptide which inhibits the catalytic activity of myeloperoxidase in human neutrophils. Teg49 was found to regulate spn mRNA post-transcriptionally in strain SH1000 through 9-nt base-pairing between hairpin loop 2 of Teg49 and an exposed bulge of the spn mRNA. Mutations of the Teg49 binding site disrupted the repression of spn, leading to reduced degradation, and increased half-life of spn mRNA in the Teg49 mutant. The spn-Teg49 interaction was also confirmed with a synonymous spn mutation to yield enhanced spn expression in the mutant vs. the parent. The Teg49 mutant with increased spn expression exhibited enhanced resistance to MPO activity in vitro. Killing assays with human neutrophils showed that the Teg49 mutant was more resistant to killing after phagocytosis. Altogether, this study shows that Teg49 in S. aureus has a distinct and important regulatory profile whereby this sRNA modulates resistance to myeloperoxidase-mediated killing by human neutrophils.

中文翻译：

金黄色葡萄球菌中小 RNA Teg49 对中性粒细胞髓过氧化物酶抑制剂 SPIN 的调控

Teg49 是一种金黄色葡萄球菌反式作用调节 sRNA，源自sarA P3 转录本的裂解。我们在这里通过 RNA-Seq 表明，Teg49 中的 5' 三叉戟样结构在转录（直接和间接）上调节 22 个不同于sarA的基因。其中，注意到 Teg49 抑制spn，编码 102 个残基的前蛋白，产生成熟的 73 个残基肽，抑制人嗜中性粒细胞中髓过氧化物酶的催化活性。发现Teg49 通过 Teg49 的发夹环 2 和 spn 的暴露凸起之间的 9-nt 碱基配对在菌株 SH1000 中转录后调节spn mRNAmRNA。Teg49 结合位点的突变破坏了 spn 的抑制，导致降解减少，并增加了Teg49突变体中 spn mRNA 的半衰期。spn -Teg49相互作用也通过同义 spn 突变得到证实，以在突变体与亲本中产生增强的spn表达。spn 表达增加的Teg49突变体在体外表现出对 MPO 活性的增强抗性。人类嗜中性粒细胞的杀伤试验表明，Teg49 突变体在吞噬后更能抵抗杀伤。总之，这项研究表明金黄色葡萄球菌中的 Teg49具有独特且重要的调节特征，由此该 sRNA 调节对髓过氧化物酶介导的人嗜中性粒细胞杀伤的抗性。

更新日期：2022-05-16

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